Mother Jones began taking shape in 1974 when the Watergate scandal was demonstrating how investigative reporting could weaken and oust a Republican President elected by an overwhelming majority. Its genesis was a failed attempt to save the reigning radical magazine of the day, Ramparts. Ramparts editor David Horowitz had put together a team consisting of labor journalist Paul Jacobs, leftist entrepreneur Richard Parker, and leftist millionaire Adam Hochschild to take over Ramparts from its retiring editors, Horowitz and Peter Collier. When the trio had a falling out with Ramparts staffers, they elected to leave and create their own magazine, which became Mother Jones.

The magazine was launched in February 1976.

Mother Jones focuses heavily on the evils of capitalism and the alleged desirability of government control over business. On a global level, the magazine reserves its harshest condemnations for the U.S. and Israel, and is staunchly supportive of Marxist regimes like Fidel Castro's Cuba.

In 1986 Mother Jones hired a young Michigan underground newspaper founder named Michael Moore as its Editor. Five months later, Moore was fired after he rejected an article by socialist Paul Berman, a piece that Moore claimed was "unfairly critical" of the Sandinista dictatorship in Nicaragua. Moore sued, claiming wrongful dismissal. He pocketed $58,000 in an out-of-court settlement of his lawsuit, then used the money to produce his first film documentary, "Roger and Me."

The Mother Jones magazine and website are owned by the non-profit, tax-exempt Foundation for National Progress (FNP), a 501(c)(3) "public-interest media organization." FNP has been supported by other left-leaning foundations, among them the Arca Foundation, the David and Lucile Packard Foundation, the Irving Harris Foundation, the Joyce Foundation, Kansas City Community Foundation, the Lannan Foundation, the Park Foundation, the Bill Moyers-run Schumann Center for Media and Democracy, and the Streisand Foundation. In 2000, the magazine, website and Foundation took in (from grants, donations, subscriptions, newsstand sales, rental of its mailing lists. and advertising) nearly $6 million. From 2002 to 2004, FNP received $410,000 in foundation grants.

In April 2013, Mother Jones released secretly taped recordings and a transcript of a February 2 opposition-research meeting that Republican Senator Mitch McConnell had held with his staff. McConnell’s re-election campaign denounced the magazine's “Nixonian tactics.” Speculating that McConnell’s campaign may have been bugged extensively, Republicans suggested that the FBI could get involved in investigating the matter.